The extremely large numbers of conformations accessible to peptides of size 10 to 20 residues, make them difficult to consider both theoretically and experimentally. Comprehensive sets of their conformations are nearly impossible to consider. A new approach to combine calculations with specific information has been developed. The constraining information could originate either from experiment or from a molecular model with specified interactions. This approach to consider random peptide conformations with constraints has been formulated in the context of helix-coil theory. In other studies of the use of NMR data as constraints, ways to perform thorough conformational searches have been developed in order to view all conformations that are consistent with the experimental data. The number of such alternative forms provides a direct measure of the extent of structural under-determination. Protein surfaces are being examined in order to develop methods to specify likely binding sites for peptides. This is the first stage in a new approach to inhibitor design to develop new therapeutic agents.